ApiAP2 Gene-Network Regulates Gametocytogenesis in Plasmodium Parasites

Figure 3

ApiAP2 gene-network regulates gametocytogenesis in Plasmodium species. (a) Precommitment AP2-G2 represses sexual stage genes preventing the initiation of gametocytogenesis. AP2-G5 binds to ap2-g and directly inhibits its expression. (b) Sexual commitment AP2-G3/FG transmits cytoplasmic signals of sexual switch into the nucleus. AP2-G5 is evicted from the exogenic body and upstream promoter of ap2-g. HP1 is also evicted from the H3K36me3 repressive complex and thus initiates gametocyte commitment. (c) Sexual conversion AP2-G binds to its own promoter and increases ap2-g expression which drives the conversion of sexual commitment rings into early-stage gametocytes. Time-point stabilization of ap2-g expression determines the route of sexual conversion; next cycle conversion (NCC) or same cycle conversion (SCC) pathways (not shown in the diagram, but described in detail in the text). GEXP5 is expressed concomitantly with AP2-G to regulate the sexual conversion process. (d, f) Sexual maturation. During stage I, AP2-G increases the expression of early-stage (EG) gametocyte genes. AP2-O3 regulates the maturation of female gametocytes between stages II-III. AP2-G2 putatively represses the expression of late gametocyte-stage genes to prevent their premature expression but is derepressed at stages IV-V. AP2-G2/FG controls late-stage sexual dimorphism of female gametocytes (in P. berghei) or the maturation of both male and female gametocytes from stage II down through to stage V. “” indicates possible different phenotypes among different Plasmodium species; HP1: heterochromatin protein 1; Hda2: histone deacetylase 2; H3K9me3: Histone 3 lysine 9 trimethylation; GDV1: gametocyte development 1. Schematic created with Biorender.com.

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